Long-term serotonin administration leads to higher bone mineral density, affects bone architecture, and leads to higher femoral bone stiffness in rats

New evidence suggests a control of bone mass by the central nervous system. We have previously shown that functional serotonin receptors are present in bone cells and that serotonin stimulates proliferation of osteoblast precursor cells in vitro. In the present study we investigated the effects of serotonin on bone tissue in vivo. Ten, 2-month-old female Sprague-Dawley rats were injected with serotonin subcutaneously (s.c.) (5 mg/kg) once daily for 3 months, controls received saline. Using microdialysis and HPLC, free circulating serotonin levels were measured. DXA scans were made after 3 months of serotonin administration. Bone architecture and mechanical properties were investigated by micro-computed tomography (microCT), histomorphometry, and mechanical testing. A long-lasting hyperserotoninemia with a >10-fold increase in serotonin appeared. Total body BMD was significantly higher (0.1976+/-0.0015 vs. 0.1913+/-0.0012 g/cm2) in rats receiving serotonin. Cortical thickness (Ct.Th) measured by microCT analysis was also higher, whereas trabecular bone volume (BV) was lower. Interestingly, the perimeter and cross-sectional moment of inertia (MOI), a proxy for geometrical bone strength, were the same in both groups. These data suggest that serotonin reduces resorption or/and increases apposition of endosteal bone. Mechanical testing showed that femoral stiffness was higher in serotonin-dosed animals. The energy absorption also seemed slightly, but not significantly higher. In conclusion, hyperserotoninemia led to a higher BMD, altered bone architecture and higher femural bone stiffness in growing rats, demonstrating that serotonin may have important effects on bone in vivo.